Studies of the chick ciliary ganglion using electrophysiological, molecular, and microscopic techniques are proposed to test two hypotheses. One hypothesis is that extrasynaptic AChRs influence the extent of neuronal survival and maturation during development. A second hypothesis is that presynaptic AChRs, implicated in ACh release, are influenced by neuropeptide-generated signals thereby providing a means of modulating release from nerve terminals. Alpha7 AChRs have been found in ciliary ganglion neurons in addition to synaptic a3 AChRs on the same neurons. Dr. Margiotta proposes to investigate the role of a7 subunits in development by measuring a7 transcripts during the course of development, testing the effects of AChR blockade on neuron survival, maturation, and synapse formation. Presynaptic AChRs will be sought on terminals of cultured and freshly isolated neurons and tested for their effects on ACh release. To examine if synaptic and presynaptic AChRs are targeted by different intracellular signals, the subtype-specific effects of activating separate signaling pathways by neuropeptides will then be elucidated.